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John P Dalton - One of the best experts on this subject based on the ideXlab platform.
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the Fasciola Hepatica genome gene duplication and polymorphism reveals adaptation to the host environment and the capacity for rapid evolution
Genome Biology, 2015Co-Authors: Krystyna Cwiklinski, John P Dalton, Philippe J Dufresne, James La Course, D J L Williams, Jane E Hodgkinson, Steve PatersonAbstract:Background The liver fluke Fasciola Hepatica is a major pathogen of livestock worldwide, causing huge economic losses to agriculture, as well as 2.4 million human infections annually.
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immunomodulatory molecules of Fasciola Hepatica candidates for both vaccine and immunotherapeutic development
Veterinary Parasitology, 2013Co-Authors: John P Dalton, Grace Mulcahy, Mark W Robinson, Sandra M Oneill, Sheila DonnellyAbstract:The liver fluke, Fasciola Hepatica, causes fascioliasis in domestic animals (sheep, cattle), a global disease that is also an important infection of humans. As soon as the parasite invades the gut wall its interaction with various host immune cells (e.g. dendritic cells, macrophages and mast cells) is complex. The parasite secretes a myriad of molecules that direct the immune response towards a favourable non-protective Th2-mediate/regulatory environment. These immunomodulatory molecules, such as cathepsin L peptidase (FhCL1), are under development as the first generation of fluke vaccines. However, this peptidase and other molecules, such as peroxiredoxin (FhPrx) and helminth defence molecule (FhHDM-1), exhibit various immunomodulatory properties that could be harnessed to help treat immune-related conditions in humans and animals.
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the silencing of cysteine proteases in Fasciola Hepatica newly excysted juveniles using rna interference reduces gut penetration
International Journal for Parasitology, 2008Co-Authors: Louise Mcgonigle, Terry W Spithill, John P Dalton, Angela Mousley, Nikki J Marks, Gerard Brennan, Tim A Day, Aaron G MauleAbstract:Probing protein function in parasitic flatworms is hampered by the difficulties associated with the development of transgenic approaches. Although RNA interference (RNAi) in schistosomes shows much promise, it has not been reported in other trematodes. Here, we show the successful silencing of the cysteine proteases cathepsin B and L in the infective stage of Fasciola Hepatica newly excysted juveniles (NEJs). Silencing resulted in marked reductions in target transcript levels and significant diminution in the encoded proteins in the gut. RNAi of either enzyme in NEJs induced transient, abnormal locomotory phenotypes, and significantly reduced penetration of the rat intestinal wall.
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vaccines against the zoonotic trematodes schistosoma japonicum Fasciola Hepatica and Fasciola gigantica
Parasitology, 2006Co-Authors: Donald P Mcmanus, John P DaltonAbstract:Schistosoma japonicum , Fasciola Hepatica and F. gigantica are digenetic trematodes and, therefore, possess similar life cycles. While schistosomiasis japonica has for a long time been recognised as a major disease of both humans and animals, infection with fasciolids has only been considered of relevance to animals. However, a number of recent reports indicate that fasciolosis is becoming a serious public health problem, especially in South America, Egypt and Iran (sporadic cases are also on the increase throughout Europe). Vaccines targeted at animals could play an important role in controlling these three diseases in animals and, by blocking transmission of infection, have a concurrent beneficial effect on disease in humans. Approaches towards identifying and producing vaccines against these parasites are similar and are discussed in this reveiw.
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a bolus for the administration to cattle of metacercariae of the liver fluke Fasciola Hepatica
Journal of Helminthology, 1995Co-Authors: Stuart John Andrews, John P Dalton, Sharon Mcgonigle, Angela M Smith, D Clery, Grace MulcahyAbstract:A gelatin-agar bolus, designed and developed for the administration of metacercariae of the liver fluke Fasciola Hepatica , was evaluated in adult Holstein Friesian cattle. The metacercariae, enclosed within a gelatin capsule, were placed inside the bolus and delivered to each animal using an oesophageal balling gun. At slaughter, 13 weeks after challenge, an average of 25% of the challenge dose was recovered from each liver. This percentage recovery is similar to that obtained with other known methods. The new bolus, however, offers improved handling qualities. In addition, the bolus also has potential for improving a number of other techniques including those for the administration of other parasites, compounds or chemotherapeutic agents.
Terry W Spithill - One of the best experts on this subject based on the ideXlab platform.
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current threat of triclabendazole resistance in Fasciola Hepatica
Trends in Parasitology, 2016Co-Authors: Jane M Kelley, Timothy P Elliott, Travis Clarke Beddoe, G R Anderson, P J Skuce, Terry W SpithillAbstract:Triclabendazole (TCBZ) is the only chemical that kills early immature and adult Fasciola Hepatica (liver fluke) but widespread resistance to the drug greatly compromises fluke control in livestock and humans. The mode of action of TCBZ and mechanism(s) underlying parasite resistance to the drug are not known. Due to the high prevalence of TCBZ resistance (TCBZ-R), effective management of drug resistance is now critical for sustainable livestock production. Here, we discuss the current status of TCBZ-R in F. Hepatica, the global distribution of resistance observed in livestock, the possible mechanism(s) of drug action, the proposed mechanisms and genetic basis of resistance, and the prospects for future control of liver fluke infections using an integrated parasite management (IPM) approach.
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exploring the Fasciola Hepatica tegument proteome
International Journal for Parasitology, 2011Co-Authors: Alan R Wilson, Janelle M Wright, William Castroborges, Sophie Parkermanuel, Adam Dowle, Peter D Ashton, Neil D Young, Robin B Gasser, Terry W SpithillAbstract:The surface tegument of the liver fluke Fasciola Hepatica is a syncytial cytoplasmic layer bounded externally by a plasma membrane and covered by a glycocalyx, which constitutes the interface between the parasite and its ruminant host. The tegument’s interaction with the immune system during the fluke’s protracted migration from the gut lumen through the peritoneal cavity and liver parenchyma to the lumen of the bile duct, plays a key role in the fluke’s establishment or elimination. However, little is known about proteins of the tegument surface or its secretions. We applied techniques developed for the blood fluke, Schistosoma mansoni, to enrich a tegument surface membrane preparation and analyse its composition by tandem mass spectrometry using new transcript databases for F. Hepatica. We increased the membrane and secretory pathway components of the final preparation to ∼30%, whilst eliminating contaminating proteases. We identified a series of proteins or transcripts shared with the schistosome tegument including annexins, a tetraspanin, carbonic anhydrase and an orthologue of a host protein (CD59) that inhibits complement fixation. Unique to F. Hepatica, we also found proteins with lectin, cubulin and von Willebrand factor domains plus 10 proteins with leader sequences or transmembrane helices. Many of these surface proteins are potential vaccine candidates. We were hampered in collecting tegument secretions by the propensity of liver flukes, unlike blood flukes, to vomit their gut contents. We analysed both the ‘vomitus’ and a second supernatant released from haematin-depleted flukes. We identified many proteases, some novel, as well as a second protein with a von Willebrand factor domain. This study demonstrates that components of the tegumental surface of F. Hepatica can be defined using proteomic approaches, but also indicates the need to prevent vomiting if tegument secretions are to be characterised.
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the silencing of cysteine proteases in Fasciola Hepatica newly excysted juveniles using rna interference reduces gut penetration
International Journal for Parasitology, 2008Co-Authors: Louise Mcgonigle, Terry W Spithill, John P Dalton, Angela Mousley, Nikki J Marks, Gerard Brennan, Tim A Day, Aaron G MauleAbstract:Probing protein function in parasitic flatworms is hampered by the difficulties associated with the development of transgenic approaches. Although RNA interference (RNAi) in schistosomes shows much promise, it has not been reported in other trematodes. Here, we show the successful silencing of the cysteine proteases cathepsin B and L in the infective stage of Fasciola Hepatica newly excysted juveniles (NEJs). Silencing resulted in marked reductions in target transcript levels and significant diminution in the encoded proteins in the gut. RNAi of either enzyme in NEJs induced transient, abnormal locomotory phenotypes, and significantly reduced penetration of the rat intestinal wall.
Mark W Robinson - One of the best experts on this subject based on the ideXlab platform.
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immunomodulatory molecules of Fasciola Hepatica candidates for both vaccine and immunotherapeutic development
Veterinary Parasitology, 2013Co-Authors: John P Dalton, Grace Mulcahy, Mark W Robinson, Sandra M Oneill, Sheila DonnellyAbstract:The liver fluke, Fasciola Hepatica, causes fascioliasis in domestic animals (sheep, cattle), a global disease that is also an important infection of humans. As soon as the parasite invades the gut wall its interaction with various host immune cells (e.g. dendritic cells, macrophages and mast cells) is complex. The parasite secretes a myriad of molecules that direct the immune response towards a favourable non-protective Th2-mediate/regulatory environment. These immunomodulatory molecules, such as cathepsin L peptidase (FhCL1), are under development as the first generation of fluke vaccines. However, this peptidase and other molecules, such as peroxiredoxin (FhPrx) and helminth defence molecule (FhHDM-1), exhibit various immunomodulatory properties that could be harnessed to help treat immune-related conditions in humans and animals.
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the occurrence and significance of triploidy in the liver fluke Fasciola Hepatica
Parasitology, 2004Co-Authors: Hugh L Fletcher, Elizabeth M Hoey, N Orr, Alan Trudgett, Ian Fairweather, Mark W RobinsonAbstract:Karyotyping of Fasciola Hepatica samples from Britain and Ireland has identified a triploid isolate which is effectively aspermic, rendering it necessarily asexually reproducing. Considering the extensive presence of asexually reproducing diploid and triploid Fasciola in Asia it is suggested that facultative gynogenesis is widespread in this parasite. This has important implications for the population genetics and evolution of Fasciola, especially in relation to the development and spread of drug resistance, and must be considered in the mathematical modelling of this process.
Čermáková Zdeňka - One of the best experts on this subject based on the ideXlab platform.
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Cultivation of model parasite liver fluke (Fasciola Hepatica) in domestic sheep (Ovis aries) - time behavior and results
Univerzita Karlova Farmaceutická fakulta v Hradci Králové, 2018Co-Authors: Čermáková ZdeňkaAbstract:Univerzita Karlova v Praze Farmaceutická fakulta v Hradci Králové Katedra farmakologie a toxikologie Student/ka: Zdeňka Čermáková Školitel: Prof. RNDr. Jiří Lamka, CSc. Název diplomové práce: Průběh a výsledky kultivace modelového parazita motolice jaterní (Fasciola Hepatica) v ovci domácí (Ovis aries) Fasciolóza je parazitární onemocnění způsobené motolicí jaterní (Fasciola Hepatica). Tato parazitóza je významným onemocněním hospodářských zvířat, volně žijící zvěře a v některých částech světa i člověka. Působí snížení užitkovosti a plodnosti zvířat, úbytky hmotnosti a vysoké ekonomické ztráty v chovech. Cílem této práce bylo detailně popsat průběh experimentální infekce ovcí infikovaných metacerkáriemi F. Hepatica. Konkrétně byly sledovány změny v krevním obrazu, vylučování vajíček trusem a odpovědi imunitního systému nakažených jedinců. Zjištěné hodnoty byly porovnány s již provedenými studiemi. Pro průkaz fasciolózy u experimentálně nakažených ovcí byla využita koprologická sedimentační metoda, diferenciální stanovení leukocytů z krevních nátěrů, stanovení hematokritu a imunologická metoda ELISA (enzyme-linked immunosorbent assays). K experimentu byly použity tři jehnice plemene Texel infikované 200 metacerkáriemi. Diferenciální diagnostika leukocytů poskytla nejčasnější průkaz o průběhu a stavu...Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zdeňka Čermáková Supervisor: Prof. RNDr. Jiří Lamka, CSc. Title of diploma thesis: The progression and results of the model parasite culturing liver fluke (Fasciola Hepatica) in sheep (Ovis aries) Fasciolosis is a parasitic disease caused by liver fluke (Fasciola Hepatica). This parasitosis is a significant disease in livestock, wild animals and in some parts of the world in humans. It causes a decrease in livestock performance and fertility, weight loss and high economic losses in livestock. The aim of this work was to describe in detail the course of artificial infection of sheep infected with F. Hepatica metacercaria. Specifically, changes in blood count, egg excretion, and response of the immune system of infected individuals were monitored. The observed values were compared with the studies already performed. The demonstration of fasciolosis in artificially infected sheep was performed using the coprological sedimentation method, the differential determination of leukocytes from the blood layers, the determination of hematocrit and the immunological method ELISA (enzyme-linked immunosorbent assays). Three lambs of Texel breeds infected with 200 metacercaria were used for the...Katedra farmakologie a toxikologieDepartment of Pharmacology and ToxicologyFaculty of Pharmacy in Hradec KrálovéFarmaceutická fakulta v Hradci Králov
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Cultivation of model parasite liver fluke (Fasciola Hepatica) in domestic sheep (Ovis aries) - time behavior and results
2018Co-Authors: Čermáková ZdeňkaAbstract:Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zdeňka Čermáková Supervisor: Prof. RNDr. Jiří Lamka, CSc. Title of diploma thesis: The progression and results of the model parasite culturing liver fluke (Fasciola Hepatica) in sheep (Ovis aries) Fasciolosis is a parasitic disease caused by liver fluke (Fasciola Hepatica). This parasitosis is a significant disease in livestock, wild animals and in some parts of the world in humans. It causes a decrease in livestock performance and fertility, weight loss and high economic losses in livestock. The aim of this work was to describe in detail the course of artificial infection of sheep infected with F. Hepatica metacercaria. Specifically, changes in blood count, egg excretion, and response of the immune system of infected individuals were monitored. The observed values were compared with the studies already performed. The demonstration of fasciolosis in artificially infected sheep was performed using the coprological sedimentation method, the differential determination of leukocytes from the blood layers, the determination of hematocrit and the immunological method ELISA (enzyme-linked immunosorbent assays). Three lambs of Texel breeds infected with 200 metacercaria were used for the..
Aaron G Maule - One of the best experts on this subject based on the ideXlab platform.
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the silencing of cysteine proteases in Fasciola Hepatica newly excysted juveniles using rna interference reduces gut penetration
International Journal for Parasitology, 2008Co-Authors: Louise Mcgonigle, Terry W Spithill, John P Dalton, Angela Mousley, Nikki J Marks, Gerard Brennan, Tim A Day, Aaron G MauleAbstract:Probing protein function in parasitic flatworms is hampered by the difficulties associated with the development of transgenic approaches. Although RNA interference (RNAi) in schistosomes shows much promise, it has not been reported in other trematodes. Here, we show the successful silencing of the cysteine proteases cathepsin B and L in the infective stage of Fasciola Hepatica newly excysted juveniles (NEJs). Silencing resulted in marked reductions in target transcript levels and significant diminution in the encoded proteins in the gut. RNAi of either enzyme in NEJs induced transient, abnormal locomotory phenotypes, and significantly reduced penetration of the rat intestinal wall.